This chapter focuses on drug-induced disease resulting from adverse drug events (ADEs) caused by either inherent drug toxic effects, drug–disease adverse interactions or as a consequence of unintentional drug–drug interactions. Additional topics covered in this chapter include a discussion about the diagnosis of drug-induced disease, an overview of the Food and Drug Administration (FDA) process for drug approval, postmarketing surveillance of ADEs, and the role of the medical toxicologist in the discovery, reporting, and prevention of ADEs.
ADEs are defined as untoward effects or outcomes associated with use of a drug. In this chapter, the word "drug" will be used for a -pharmaceutical product and includes prescription and nonprescription medications, and dietary supplements.
In the United States, all new prescription and nonprescription -medications must be shown to be both safe and effective in order to achieve approval by the FDA, a prerequisite for marketing and sale. Dietary supplements fall outside of this legal requirement.
Prior to 1900, there was no requirement for a drug or medical device manufacturer to demonstrate that the product actually worked (efficacy), was safe when used as directed, or was made to be within precise specifications. In addition, no laws existed that required labeled claims be proven valid. Anyone could sell any product desired and it was left to the consumer or healthcare worker to determine if the -products actually worked and were safe. Initiation of medicinal product regulation and the overall evolution of the US drug law and regulations are closely linked to specific medical product disasters that occurred during the 20th century in the United States. Relatively recent changes in US drug approval law further changed drug review timelines and prioritization of drug application reviews.
Examples of the pre-1900 regulation of medicinal products include the lack of a legal requirement for a company to test a product for safety or efficacy or even to make valid claims in the drug label. Products such as aspirin-containing heroin were sold as cough syrup. Wine with cocaine was marketed to enhance sales of the alcoholic beverage. Further, there was no legal requirement for systematic testing of products to determine content or the presence of possible adulterants in product formulations. The Food and Drug Act of 1906 required pharmaceutical manufacturers to meet a standard for the concentration and purity of the drugs they marketed. However, the burden of proof was on the FDA to show that the drug was incorrectly labeled or that the advertising or label was false or misleading.
The Food, Drug and Cosmetic Act of 1938 resulted from a tragedy in which more than 100 patients (mostly children) died from poisoning by an excipient of an oral solution of sulfanilamide. A pharmaceutical company, in an attempt to improve the palatability of a sulfanilamide product for pediatric formulations, introduced the solvent diethylene glycol into the formulation. Diethylene glycol is a sweet-tasting but nephrotoxic hydrocarbon. Only after almost ...